Radical Hydrostannylation, Pd(0)-Catalyzed Hydrostannylation, Stannylcupration of Propargyl Alcohols and Enynols:  Regio- and Stereoselectivities

Betzer, Jean‐François; Delaloge, Francette; Muller, B.; Pancrazi, Ange; Prunet, Joëlle

doi:10.1021/jo9710339

Cited by 198 publications

(144 citation statements)

References 26 publications

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“…During the course of hydrostannlylation, the formation of undesired regioisomer could not be supressed, thus leading to only moderate yield. Other approaches such as hydrozirconation [21] and stannylcupration [22] gave complex mixtures of products. The final building block 5 constitutes for the eastern part of the macrolactone, incorporating the dienoic acid moiety (Scheme 4).…”

Section: Communicationmentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

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Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18-membered macrolactone is reported herein. The key reactions include ring-closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium-sized fragments, thus leading to a flexible yet convergent synthetic route. COMMUNICATION Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)Hideki Miyatake-Ondozabal, Elias Kaufmann and Karl Gademann* Dedication ((optional)) Abstract: Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have an excellent bactericidal activity against multi-drug resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has ever been reported to date. Herein, we report the enantioselective synthesis of the central 18-membered macrolactone. The noteworthy reactions include ringclosing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis comprises of three medium sized fragments leading to a flexible yet convergent synthetic route.

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Section: Communicationmentioning

confidence: 99%

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

2014

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“…Sc(OTf) 3 was obtained from Sigma-Aldrich and was dried under vacuum at 150°C for 12 h. Pd(PPh 3 ) 4 and B(C 6 F 5 ) 3 were obtained from Strem Chemicals; Bu 3 SnCl, CsF, DIBAL-H, nBuLi, NaHMDS, trans-cinnamaldehyde, 2,6-di-tert-butyl-4-methylpyridine, Cu(OTf) 2 , Me 3 Al, Me 2 AlCl, BF 3 ·OEt 2 , AlI 3 , TfOH, and 2,6-bis[(4R)-4-phenyl-2-oxazolinyl]pyridine were obtained from Sigma-Aldrich; these reagents were used without further purification. Copper(I) thiophene-2-carboxylate, 6 (iodomethyl)triphenylphosphonium iodide, 16 a-iodocinnamaldehyde (6), 17 abromocinnamaldehyde (9), 18 ethyl 2-tributylstannyl-2-butenoate (15), 4 4-iodo-2-methyl-1-phenyl-1,3-butadiene (18), 4 manganese dioxide, 19 phenylaluminum dichloride, 20 2-tributylstannylpropenol (22), 21 2-tributylstannyl-2-cyclopentenone (33), 4 hexatriene 2, 4 and cyclohexadiene 36, 4 were synthesized according to literature proce- dures. Characterization data for these compounds agree with literature values.…”

Section: Discussionmentioning

confidence: 99%

On the Development of Catalytic Carba-6π Electrocyclizations

et al. 2010

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Hexatriene substrates substituted in the 2-position with carbonyl groups were studied in the context of catalytic 6π electrocyclizations. The nature of the carbonyl group and the substitution pattern on the hexatriene have significant effects on the ability of these substrates to succumb to catalysis. A novel 2-formyl hexatriene dimerization was observed. The first example of a catalytic asymmetric carba-6π electrocyclization is reported along with the discovery of an unusual kinetic resolution via a catalytic photochemical electrocyclic ring-opening.Key words: electrocyclic reactions, catalysis, dimerization, asymmetric catalysis, kinetic resolution.The ability to catalyze pericyclic reactions has greatly increased their synthetic utility and has allowed for the development of asymmetric versions. Among the different types of these reactions, Diels-Alder cycloadditions, Claisen rearrangements, and Nazarov cyclizations have been rendered asymmetric by using a variety of chiral Lewis acids, Brønsted acids and aminocatalysts. 1,2 Our group has contributed to this topic by introducing 2-alkoxy-1,4-pentadien-3-ones as excellent substrates for Nazarov cyclizations, which have yielded the first highly enantioselective examples of these 4π electrocyclizations. 2 More recently, 6π electrocyclizations have come into focus. In 2009, List and Smith independently reported asymmetric catalysis in aza-6π electrocyclizations. 3 Prior to this, we demonstrated that carba-6π electrocyclizations could be catalyzed with Lewis acids (Scheme 1). 4,5 Using esters (e.g., 1) and ketones (e.g., 2) as Lewis bases and Me 2 AlCl as a Lewis acid, we showed that rate accelerations up to 55-fold could be achieved. Our experimental results were accompanied by theoretical calculations on simple aldehydes, such as 3, which indeed showed that placement of a formyl group in the 2-position should result in significant rate accelerations upon binding of a Lewis acid or a proton.It is generally believed that aldehydes are preferred substrates for asymmetric Lewis acid catalyzed reactions, since the geometry of their complexation is well-defined. In addition, unsaturated aldehydes, such as 3, allow for aminocatalysis, which is more problematic with ketones due to their decreased electrophilicity and increased steric hindrance. We have therefore investigated 2-formyl hexatrienes in the context of catalytic 6π electrocyclizations. Herein, we report on our experiences with these substrates and provide an update on our continued studies of catalytic and asymmetric catalytic carba-6π electrocyclizations. In the course of these investigations, we have established that certain substituents on the hexatriene system are required to promote electrocyclizations and prevent side reactions, such as double bond isomerizations or Prins-type cyclizations. Powerful new Lewis acid catalysts have been identified that have led to rate accelerations an order of magnitude higher than previously described. In addition, we have launched preliminary investigations ...

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“…Under Mitsunobu conditions this was converted into the thioacetate 28 (85 % yield). Next, propargyl alcohol (25) was cis-hydrostannylated [31] using (Bu 3 Sn)BuCu(CN)Li 2 . [28] The resulting (tributylstannyl)allyl alcohol (84 % yield) was converted into the known [32] [34] -the heptatrienyldistannane 13 was formed as a 95:5 trans/cis mixture (78 % yield).…”

Section: Jochen Burghart and Reinhard Brückner*mentioning

confidence: 99%

Total Synthesis of Naturally Configured Pyrrhoxanthin, a Carotenoid Butenolide from Plankton

Burghart

Brückner

2008

Angew Chem Int Ed

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Radical Hydrostannylation, Pd(0)-Catalyzed Hydrostannylation, Stannylcupration of Propargyl Alcohols and Enynols: Regio- and Stereoselectivities

Cited by 198 publications

References 26 publications

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)

On the Development of Catalytic Carba-6π Electrocyclizations

Total Synthesis of Naturally Configured Pyrrhoxanthin, a Carotenoid Butenolide from Plankton

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